UniProtKB/Swiss-Prot Q96T54: Variant p.Gly88Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 88 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Glycine (G) to Arginine (R) at position 88 (G88R, p.Gly88Arg). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: Change from glycine (G) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

• Lowest score: -4 (low probability of substitution).
• Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description: Found in a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation; results in 3-fold increased current conductance when compared to wild-type; leads to more pronounced afterhyperpolarization and markedly slowed beating frequency and upstroke velocity when expressed in spontaneously beating sinoatrial node-like cardiomyocytes; no effect on channel subcellular localization; acts as a dominant active on wild-type subunit. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs141016843 [ dbSNP | Ensembl ]

Sequence information

Variant position: 88 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 332 The length of the canonical sequence.
Location on the sequence: CLDRPALDSLIRDVVQAYKN G ASLLSNTTSMGRWELVGSFF The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

• Type: the type of sequence feature.
• Positions: endpoints of the sequence feature.
• Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 332	Potassium channel subfamily K member 17
Glycosylation	94 – 94	N-linked (GlcNAc...) asparagine
Disulfide bond	68 – 68	Interchain (with C-68)
Mutagenesis	88 – 88	G -> A. Slightly increased current conductance when compared to wild-type.
Mutagenesis	88 – 88	G -> E. 3.6-fold increased current conductance when compared to wild-type.
Mutagenesis	88 – 88	G -> K. 7.3-fold increased current conductance when compared to wild-type.

Literature citations

Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder.
Friedrich C.; Rinne S.; Zumhagen S.; Kiper A.K.; Silbernagel N.; Netter M.F.; Stallmeyer B.; Schulze-Bahr E.; Decher N.;
EMBO Mol. Med. 6:937-951(2014)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT ARG-88; MUTAGENESIS OF GLY-88;